Excitotoxicity is the pathological process by which nerve cells may be damaged or killed by glutamate and similar substances. Excitotoxicity may be involved in spinal cord injury, stroke, traumatic brain injury and neurodegenerative diseases of the central nervous system (CNS) such as multiple sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, alcoholism or alcohol withdrawal and Huntington's disease. Other common conditions that cause excessive glutamate concentrations around neurons are hypoglycemia and status epilepticus.
Stroke may result due to a number of mechanisms. Cerebral thrombosis and cerebral embolism may result from blood clots that block an artery supplying the brain, which are the cause of most strokes. Subarachnoid hemorrhage and intracerebral hemorrhage occur when a blood vessel bursts in or around the brain. Accordingly, strokes may be ischemic (i.e. cerebral thrombosis or cerebral embolism) or hemorrhagic (i.e. subarachnoid hemorrhage or intracerebral hemorrhage) in nature.
A blood clot or thrombus formation is often the result of atherosclerosis of a brain artery. A transient ischemic attack (TIA) is also referred to as a mini-stroke and is characterized by a temporary blood flow interruption and often precedes a stroke.
An embolism occurs when a blood clot becomes dislodged from a remote location in the circulatory system and subsequently becomes lodged in an artery supplying the brain (for example, in the brain or in the neck). Cerebral embolisms often occur in patients with atrial fibrillation, where the upper chambers (atria) of the heart beat weakly and rapidly and the blood in the atria is not completely emptied. The blood which stagnates is more susceptible to clot formation.
A hemorrhage or bleeding, occurs when a blood vessel breaks. A break in a blood vessel may result from trauma or excess internal pressure. The vessels most likely to break are those with preexisting defects such as an aneurysm.
An intracerebral hemorrhage occurs in the vessels of the brain, while subarachnoid hemorrhage affects arteries at the brain's surface (i.e. protective arachnoid membrane).
All of the above stroke mechanisms may result in the death of brain cells, which in turn triggers a chain reaction in which toxic chemicals created by cell death may damage neighbouring cells. Cells in the affected region of the brain often die because they no longer receive oxygen and nutrients from the blood and due to excessive glutamate concentrations, leading to the symptoms and disabilities of stroke patients. Stroke is the third leading cause of death in North America, and the leading cause of disability.